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Published on: June 13, 2016
Dysregulation in microRNA expression in peripheral blood mononuclear cells of sepsis patients is associated with
Juhua Zhou1, Hina Chaudhry2, Yin Zhong3
1Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA; Institute for Tumor Immunology, Ludong University School of Life Sciences, Yantai, Shandong 264025, PR China.
Abstract:
Sepsis is a major cause of death worldwide. It triggers systemic inflammation, the role of which remains unclear. In the current study, we investigated the induction of microRNA (miRNA) during sepsis and their role in the regulation of inflammation. Patients, on days 1 and 5 following sepsis diagnosis, had reduced T cells but elevated monocytes. Plasma levels of IL-6, IL-8, IL-10 and MCP-1 dramatically increased in sepsis patients on day 1. T cells from sepsis patients differentiated primarily into Th2 cells, whereas regulatory T cells decreased. Analysis of 1163 miRNAs from PBMCs revealed that miR-182, miR-143, miR-145, miR-146a, miR-150, and miR-155 were dysregulated in sepsis patients. miR-146a downregulation correlated with increased IL-6 expression and monocyte proliferation. Bioinformatics analysis uncovered the immunological associations of dysregulated miRNAs with clinical disease. The current study demonstrates that miRNA dysregulation correlates with clinical manifestations and inflammation, and therefore remains a potential therapeutic target against sepsis.
Insights
Sepsis causes systemic inflammation and immune cell changes. This study found microRNA (miRNA) dysregulation in sepsis patients, linking specific miRNAs to inflammation and suggesting potential therapeutic targets.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Sepsis is a leading global cause of mortality.
- Sepsis-induced systemic inflammation plays a critical role, but its mechanisms are not fully understood.
- MicroRNAs (miRNAs) are emerging as key regulators of cellular processes, including inflammation.
Purpose of the Study:
- To investigate miRNA induction during sepsis.
- To elucidate the role of miRNAs in regulating sepsis-induced inflammation.
- To identify potential miRNA-based therapeutic targets for sepsis.
Main Methods:
- Analysis of T cell and monocyte populations in sepsis patients.
- Quantification of plasma inflammatory cytokines (IL-6, IL-8, IL-10, MCP-1).
- miRNA profiling of peripheral blood mononuclear cells (PBMCs) from sepsis patients and healthy controls.
- Bioinformatics analysis to correlate miRNA dysregulation with clinical and immunological data.
Main Results:
- Sepsis patients exhibited reduced T cells and elevated monocytes.
- Significant increases in plasma IL-6, IL-8, IL-10, and MCP-1 were observed.
- Specific miRNAs, including miR-146a, were found to be dysregulated.
- Downregulation of miR-146a correlated with increased IL-6 and monocyte proliferation.
Conclusions:
- miRNA dysregulation is a significant feature of sepsis.
- Altered miRNA expression is closely associated with clinical manifestations and inflammatory responses in sepsis.
- Targeting dysregulated miRNAs presents a promising therapeutic strategy for sepsis management.
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